Fernando Rodrigo Carlini, de Carvalho Fabrício, Leme Adriana Franco Paes, Colleoni Gisele Wally Braga
Department of Experimental and Clinical Oncology, Discipline of Hematology and Hemotherapy, Federal University of São Paulo, UNIFESP, São Paulo, Brazil.
Laboratory of Mass Spectrometry, Laboratory of National Biosciences, LNBio, National Council for Research in Energy and Materials (CNPEM), Campinas, Brazil.
Front Oncol. 2021 Mar 23;11:563384. doi: 10.3389/fonc.2021.563384. eCollection 2021.
Although the "seed and soil" hypothesis was proposed by Stephen Paget at the end of the 19th century, where he postulated that tumor cells (seeds) need a propitious medium (soil) to be able to establish metastases, only recently the tumor microenvironment started to be more studied in the field of Oncology. Multiple myeloma (MM), a malignancy of plasma cells, can be considered one of the types of cancers where there is more evidence in the literature of the central role that the bone marrow (BM) microenvironment plays, contributing to proliferation, survival, migration, and drug resistance of tumor cells. Despite all advances in the therapeutic arsenal for MM treatment in the last years, the disease remains incurable. Thus, studies aiming a better understanding of the pathophysiology of the disease, as well as searching for new therapeutic targets are necessary and welcome. Therefore, the present study aimed to evaluate the protein expression profiling of mononuclear cells derived from BM of MM patients in comparison with these same cell types derived from healthy individuals, in order to fill this gap in MM treatment. Proteomic analysis was performed using the mass spectrometry technique and further analyses were done using bioinformatics tools, to identify dysregulated biological pathways and/or processes in the BM microenvironment of patients with MM as a result of the disease. Among the pathways identified in this study, we can highlight an upregulation of proteins related to protein biosynthesis, especially chaperone proteins, in patients with MM. Additionally, we also found an upregulation of several proteins involved in energy metabolism, which is one of the cancer hallmarks. Finally, with regard to the downregulated proteins, we can highlight mainly those involved in different pathways of the immune response, corroborating the data that has demonstrated that the immune system of MM is impaired and, therefore, the immunotherapies that have been studied recently for the treatment of the disease are extremely necessary in the search for a control and a cure for these patients who live with the disease.
尽管“种子与土壤”假说是19世纪末由斯蒂芬·佩吉特提出的，他假定肿瘤细胞（种子）需要适宜的介质（土壤）才能形成转移，但直到最近肿瘤微环境才开始在肿瘤学领域得到更多研究。多发性骨髓瘤（MM）是一种浆细胞恶性肿瘤，可被视为文献中更多证据表明骨髓（BM）微环境起核心作用的癌症类型之一，它有助于肿瘤细胞的增殖、存活、迁移和耐药性。尽管近年来MM治疗的治疗手段有了诸多进展，但该疾病仍然无法治愈。因此，旨在更好地理解该疾病病理生理学以及寻找新治疗靶点的研究是必要且受欢迎的。因此，本研究旨在评估MM患者骨髓来源的单核细胞与健康个体来源的相同细胞类型的蛋白质表达谱，以填补MM治疗中的这一空白。使用质谱技术进行蛋白质组学分析，并使用生物信息学工具进行进一步分析，以确定MM患者骨髓微环境中因疾病导致的失调生物途径和/或过程。在本研究确定的途径中，我们可以突出显示MM患者中与蛋白质生物合成相关的蛋白质上调，特别是伴侣蛋白。此外，我们还发现参与能量代谢的几种蛋白质上调，能量代谢是癌症特征之一。最后，关于下调蛋白质，我们可以主要突出那些参与免疫反应不同途径的蛋白质，这证实了已证明MM免疫系统受损的数据，因此，最近研究的用于治疗该疾病的免疫疗法对于寻求控制和治愈这些患有该疾病的患者极为必要。
